Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents / 中国实验血液学杂志

OBJECTIVE@#To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.@*METHODS@#The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.@*RESULTS@#170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.@*CONCLUSION@#The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Prenatal echocardiographic features and outcomes of congenital ventricular outpouching in ten fetuses / 中华围产医学杂志

Objective:To summarize the echocardiographic features and outcomes in fetuses with congenital ventricular outpouching (CVO).Methods:This retrospective study enrolled ten fetuses diagnosed with CVO by fetal echocardiography in the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital from January 2015 to April 2022. Clinical data were analyzed, including echocardiographic features, other intracardiac and extracardiac malformations, karyotypes, and pregnancy outcomes. Data were analyzed by descriptive statistics.Results:All ten cases were single, including eight ventricular diverticula and two ventricular aneurysms. Five cases had the anomaly in the left ventricular and the other five in the right. Five cases were isolated malformations, and the other five were complicated by other intra- or extracardiac malformations. A pathogenic copy number variation was detected in one case. Three pregnancies were terminated, and one was lost to follow-up. The other six fetuses were born alive and showed no obvious clinical symptoms or abnormalities in growth and development during 3-70 months of follow-up. The right ventricular diverticulum spontaneously disappeared in one case. One case with the right ventricular aneurysm was also diagnosed with noncompaction of the left ventricular myocardium by echocardiography at six months.Conclusions:Fetal CVO presents with typical echocardiographic features and can be diagnosed prenatally. Regular follow-up during pregnancy is recommended to observe the sizes of outpouchings and the occurrence of complications in fetuses with CVO after excluding other structural and chromosomal abnormalities to avoid unnecessary termination. Attention should also be paid to postnatal follow-up.

The application and insight of single-stage posterior total en bloc spondylectomy treatment on L 5 vertebrae spine tumors / 中华骨科杂志

Objective:To investigate the feasibility and technical points of single posterior total spine resection for L 5 vertebrae tumors, evaluate the effectiveness and safety of the technique, and propose a comprehensive treatment model for L 5 tumors on this basis. Methods:A retrospective analysis was performed on the data of 13 patients with L 5 vertebrae tumor who were treated by total en bloc spondylectomy (TES) through single-stage posterior approach from January 2014 to September 2021, including 4 males and 9 females. The age range was 21-65 years, with an average age of 33.85±14.24 years. Imaging examination showed isolated tumors of L 5 vertebrae without other metastases. All patients were treated with a single posterior L 5 vertebrae tumor TES by adjusting the curvature of lumbar lordosis, and the lumbar nerve root was fully dissociated. The vertebra with tumor was removed entirely and lumbar stability reconstruction via a pedicle screw system. Various parameters, including operative time, blood loss, complications, preoperative and postoperative spine sagittal parameters, Japanese Orthopaedic Association scores (JOAs), tumor control and outcome, were listed and analyzed. Results:Preoperative pathological diagnosis of 13 patients was mainly primary bone tumor including giant cell tumor in 7 cases, and invasive hemangioma, epithelioid hemangioma, aneurysmal bone cyst, chordoma, plasma cell myeloma and bone metastasis of breast cancer in 1 case. The mean operative time was 333.23±99.48 min (range 175-480 min), and the mean intraoperative blood loss was 1 407.69±676.49 ml (range 300-2 800 ml). There were no serious perioperative complications during the perioperative period. The mean follow-up was 54.92±19.29 months (range 28-84 months). JOAs improved from 13.85±3.86 points before operation to 24.31±2.16 points at 6 months after operation, and the difference was statistically significant ( t=8.19, P<0.001). Postoperative delayed wound healing occurred in 2 case. 2 patients showed numbness of the left lower limb, and 1 patient had slightly reduced plantar flexion movement. Conclusion:Single posterior TES is a good surgical method for the treatment of isolated L 5 vertebrae tumors. Although this technique is difficult, it can reduce surgical wounds and postoperative complications and good functional and oncology prognosis can be achieved.

Effect of intermittent fasting on the cognitive dysfunction induced by irradiation / 中华放射医学与防护杂志

Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.

Identification of heat stress transcription factors gene family in Setcreasea purpurea and analysis of its expression pattern under Cu2+ stress / 生物工程学报

Heat stress transcription factors (Hsf) family is one of the most important transcription factor families in plants, and plays an important role in the growth and development of plants when encountering abiotic stresses such as heat, drought, and heavy metals. In this study, 20 SpbHsf genes were identified from the full-length transcriptome database of Setcreasea purpurea, and the structure and function of the Hsf gene family were analyzed using bioinformatics tools and qRT-PCR. The results showed that all SpbHsf proteins were hydrophilic. There were 12 SpbHsf proteins located in the nucleus, and the content of α-helix and random coil in the secondary structure of all SpbHsf proteins was high. The SpbHsf genes are divided into three subfamilies, each of which contains unique conserved motifs. All SpbHsf proteins contain DBD and HR-A/B domains. Phylogenetic analysis showed that OsHsf in Oryza sativa protein had the highest homology with SpbHsf protein. All the 20 SpbHsf genes were expressed in the root tissues of S. purpurea. Among them, 8 were significantly up-regulated while 8 were significantly down-regulated under Cu2+ stress. This study may help better understand the function and expression pattern of the S. purpurea Hsf gene family.

Analysis on Clinical Characteristics and Prognosis of 47 Patients with Extranodal NK/T Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis.@*RESULTS@#Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47∶ 1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging Ⅰ/Ⅱ and stage Ⅲ/Ⅳ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×10@*CONCLUSION@#ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.

Clinical Characteristics and Prognosis Affecting-Factors of the Patients with Burkitt Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and treatment outcome of patients with Burkitt lymphoma.@*METHODS@#The clinical data of 27 patients with Burkitt Lymphoma were collected and retrospectively analyzed, the clinical characteristics, laboratory data, survival and the factors affecting the prognosis were also analyzed.@*RESULTS@#Among the 27 patients (mainly for adults), the median age was 30 (15-83) years old, the ratio of male and female was 3.5∶1. There was no EB virus infection in all the patients, 92.6% of the patients showed extranodal organs involvement, 40.7% of them were leukemic stage, 85.2% patients belonged to Ⅲ and Ⅳ stage, 74.1% patients belonged to high/high-middle risk according to IPI index. In the terms of molecular biology, five patients were treated with next-generation sequencing test, and the MYC gene mutations were detected out in alt the patients, and the most common mutations were CCND3, ID3 and TP53. The overall response rate (ORR) for all the patients was 85.2%, the complete response (CR) rate was 63.0%, and the partial response rate was 22.2%, the 5-year progression-free survival rate and overall survival rate of the patients was 76.6% and 76.6%, respectively, which showed that the efficacy of the patients in high-dose methotrexate treatment group was higher than that in the non-high high-dose methotrexate treatment group. For the patients treated with LMB89 chemotherapy, the CR was 78.6%, ORR was 100%, the 5-year survival rate was 92.9%, which was superior to the patients treated with other regimens. Auto-hematopoietic stem cell transplantation as consolidation treatment could improve the prognosis for those patients who could not tolerate high-dose chemotherapy. Univariate analysis showed that ECOG score, the level of LDH>500 U/L, WBC level, CNS involvement, short-term effect and LMB89 regimen were the risk factors affecting the prognosis of the patients.@*CONCLUSION@#The adult Burkitt lymphoma are highly aggressive. For the patients in high-dose methotrexate treatment group, especially LMB89 regimen can improve the survival of the patients, and to choose HSCT as a consolidation treatment can be a choice for those patients who could not tolerate high-dose chemotherapy.

An acute myeloid leukemia case with concurrent 11q23 anomaly and D13S319 deficiency diagnosed by combined inter- and metaphase fluorescence in situ hybridization / 中华医学遗传学杂志

Objective@#To carry out multipath cytogenetic analysis of a rare case of acute myeloid leukemia (AML) with 11q23 aberration and D13S319 deletion.@*Methods@#G+ R banding technique was used to analyze the chromosomal karyotype of the patient after 24 h of cell culture. Combined interphase and metaphase fluorescence in situ hybridization (FISH) was used to detect specific chromosomal sites for complex translocations and minor missing fragments.@*Results@#The patient was found to harbor MLL-AF10 fusion gene due to rearrangement of the mixed lineage leukemia (MLL) gene in conjunct with deletion of the D13S319 locus on chromosome 13.@*Conclusion@#Whether MLL gene rearrangement and absence of D13S319 locus has a double impact on AML should attract more attention. For AML patient with clonal abnormalities such as 13q-, del (13)(q14), -13 or der (13), FISH assay should be proof and considered to determine the size of missing fragment so as targeted therapy may be implemented.

Detection of BCR/ABL Fusion Gene and ASS1 Gene Deletion by Using Tricolor Dual-fusion Probe / 中国实验血液学杂志

OBJECTIVE@#To analyze the significance of various abnormal signal patterns appreared in CML and B-ALL patients by using BCR/ABL/ASS1 tricolor dual-fusion probe, and to explore its application value in detecting BCR/ABL fusion gene and ASS1 gene deletion.@*METHODS@#50 newly diagnosed CML patients and 50 newly diagnosed B-ALL patients were detected by fluorescence in situ hybridization (FISH) with BCR/ABL/ASS1 tricolor dual-fusion probe. Meanwhile, karyotype analysis was performed on all the patients using the 24 hours short-term culture and R-banding.@*RESULTS@#Among the 50 CML patients, Ph was found in 49 cases, 5 normal interphase karyotype was observed in 1 case. FISH detection showed that BCR/ABL fusion gene existed in all patients (100%), while the positive signal pathway showed that 1R1G2B2F was observed in 39 cases (78%), 2R1G2B1F in 2 cases (4%) and 1R1G2B1F in 6 cases (12%), simultaneous existence of 1R1G1B1F and 1R1G2B3F in 1 case (2%), 2R1G1B1F in 1 case (2%) 1R1G3B3F in 1 case (2%). FISH detection also showed that the karyotype of 6 case at ASS1 gene deletion (1R1G1B1F) all were simple t (9; 22) translocation, and other abnormalities not were observed. Among 50 cases of B-ALL, Ph was found in 13 cases, the numerical aberration and structural aberration of non t (9; 22) in 16 cases, normal karyotype in 20 cases, absence of mitotic phase in 1 case. FISH detection showed that 16 cases (32%) had BCR/ABL fusion gene including 13 cases (26%) of 1R1G2B2F, 1 case (2%) of stimultaneous exitance of 1R1G2B2F and 1R1G3B3F 1 case (2%) of 2R1G1B1F, 1 case (2%) of 1R1G3B2F. FISH detection also showed that 3 cases had BCR/ABL fusion gene, including 1 case with ASS1 gene deletion (2R1G1B1F), 1 case with classical t (9; 22) translocation (1R1G2B2F) and 1 case with BCR/ABL fusion gene and increase of ASS1 gene copy (1R1G3B3F).@*CONCLUSION@#Tricolor dual-fusion FISH probe for detecting BCR/ABL fusion gene and ASS1 gene deletion is simple, rapid, sensitive and stable. It can detect various forms of molecular fusion and avoid the false positive results due to coincidental overlap of signals generated by D-FISH probe and ES-FISH probe. In addition, this detection method not only can directly observe the presence or absence of ASS1 gene deletion, but also improve the reliability of the positive results of newly diagnosed BCR/ABL fusion gene and accuracy of monitoring results of minimal residual disease for the subsequent visit.

Effect of Bushen Tongluo Formula on Osteoporosis of Zebrafish and Study on Autophagy Mechanism of Osteoclast / 中国实验方剂学杂志

Objective::To evaluate the intervention effect of Bushen Tongluo formula on zebrafish osteoporosis model and to clarify its regulation of autophagy mechanism on osteoclast differentiation. Method::The 260 young zebrafishes (3 dpf) were selected, the zebrafish osteoporosis model was established with 25 mmol·L-1 prednisolone (Pred) for 3 days, confirming the successful model by calcein staining. The zebrafishes were divided into control group, Pred group (25 mmol·L-1), etidronate disodium (ED) group (300 mg·L-1), Bushen (BS) group (180 mg·L-1), Tongluo (TL) group (30 mg·L-1), and Bushen Tongluo (BSTL) group (210 mg·L-1), 40 tails per group. After intervened with medicine for 4 days, the calcein staining was adopted to count the vertebral bone fluorescence area of zebrafish, Real-time PCR was adopted to detect the mRNA expression of akaline phosphatase (ALP), bone morphogenetic protein 2b (BMP-2b), runt-related protein 2 (Runx2) and cathepsin K (CTSK), phosphorus and tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T-cells, cytoplasmic-1 (NFATC-1). Divided RAW264.7 cells into control, Rankl induction (10 μg·L-1), BS (180 mg·L-1), TL (30 mg·L-1), and BSTL group (210 mg·L-1) after they were cultured to 80%-90% density. The expression of actin ring was detected by phalloidin cytoskeleton staining. The mRNA expression of TRAP, CTSK and autophagy-related genes 5 (ATG5), autophagy-related genes 7 (ATG7), and ubiquitin-binding protein p62 (p62) were detected by Real-time PCR. Result::Compared with the control group in vivo, the vertebral area and ALP, BMP-2b, and Runx2 expression of zebrafish in the Pred group were significantly decreased (P<0.01), and CTSK, TRAP, and NFATC-1 expression of zebrafish were significantly increased (P<0.01). Compared with the Pred group, the vertebral area of the TL (P<0.05) and BSTL group (P<0.01) increased significantly. The expressions of ALP, BMP-2b, and Runx2 in the BS, TL, and BSTL group were significant increased (P<0.01). The expression of CTSK, TRAP, and NFATC-1 in BSTL group were significant decreased (P<0.05, P<0.01). Compared with the control group in vitro, the number of actin rings (P<0.01) and CTSK, TRAP, ATG5 (P<0.01) expression and ATG7, p62 (P<0.01) expression were significantly increased in the Rankl-induced group. Compared with the Rankl induction group, the number of actin rings and CTSK and TRAP expression were significantly decreased in the BS, TL, and BSTL group (P<0.05, P<0.01), while the expression of ATG5, ATG7, and p62 were significant decreased in the BSTL group (P<0.05). Conclusion::BSTL can significantly improve prednisolone-induced zebrafish osteoporosis and inhibit osteoclast differentiation by reducing autophagy-related gene expression.

An acute myeloid leukemia case with concurrent 11q23 anomaly and D13S319 deficiency diagnosed by combined inter- and metaphase fluorescence in situ hybridization / 中华医学遗传学杂志

OBJECTIVE@#To carry out multipath cytogenetic analysis of a rare case of acute myeloid leukemia (AML) with 11q23 aberration and D13S319 deletion.@*METHODS@#G+R banding technique was used to analyze the chromosomal karyotype of the patient after 24 h of cell culture. Combined interphase and metaphase fluorescence in situ hybridization (FISH) was used to detect specific chromosomal sites for complex translocations and minor missing fragments.@*RESULTS@#The patient was found to harbor MLL-AF10 fusion gene due to rearrangement of the mixed lineage leukemia (MLL) gene in conjunct with deletion of the D13S319 locus on chromosome 13.@*CONCLUSION@#Whether MLL gene rearrangement and absence of D13S319 locus has a double impact on AML should attract more attention. For AML patient with clonal abnormalities such as 13q-, del(13)(q14), -13 or der(13), FISH assay should be proof and considered to determine the size of missing fragment so as targeted therapy may be implemented.

Clinical Characteristics and Prognosis of 84 Elderly Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment（CGA） in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people.@*METHODS@#Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed.@*RESULTS@#The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated.@*CONCLUSION@#The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.

Effect of interleukin-37 on the pathogenesis of gout through PDZK1 protein / 中华风湿病学杂志

Objective To explore the molecular pathological mechanism of gout, and to explore the mechanism of how interleukin (IL)-37 influencing PDZK1 protein in gout through nuclear factor κB (NF-κB) pathway. Methods HK-2 cells were stimulated with inflammatory signal IL-37. The expression of PDZK1 and its subcellular localization were detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR) at different concentrations of IL-37 (defined as group A), PDTC+IL-37 (defined as group B), Wortmannin+IL-37 (defined as group C), respectively.The changes of PDZK1 protein expression in HK-2 cells were detected by adding inhibitor PDTC (NF-κB pathway inhibitor) or Wortmannin (PI3K pathway inhibitor) and inflammatory signal stimulating protein imprinting method. The comparative t test was used for statistical analysis between groups A, B and A and C. Results The average levels of PDZK1 mRNA were as follows:(group A: 28.71 ±0.35, 28.57 ±0.31, 28.78 ±0.28, 28.63 ±0.29, 28.62 ±0.19; group B: 28.71 ±0.31, 28.83 ±0.27, 28.58±0.26, 28.73±0.36, 28.68±0.35;group C:28.81±0.32, 28.91±0.29, 28.72±0.24, 28.59±0.18, 28.58±0.22). There was no significant change in PDZK1 mRNA level in group A and B. The same IL-37 was found in group A and B. The values of T were 5.73, 4.72, 4.69, 5.86 and 6.79, respectively. The P values were all greater than 0.05, and there was no significant difference between the two groups. The values of T were 6.78, 7.13, 7.47, 6.38 and 5.98 in the same IL-37 concentration groups of A and C, respectively, and the P values were all greater than 0.05, with no significant difference. The levels of PDZK1 protein in the three groups by Western blot analysis were as follows: (group A: 0.200±0.082, 0.412±0.032, 0.723±0.063, 1.202±0.021, 1.222±0.023;group B: 0.124±0.064, 0.303±0.081, 0.325±0.062, 0.223±0.071, 0.343±0.052; group C: 0.017±0.022, 0.204± 0.015, 0.187±0.053, 0.302±0.051, 0.404±0.051), The levels of PDZK1 protein in group A treated with different concentrations of IL-37 followed by the concentration of IL-37. The level of PDZK1 protein in group B increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group B was lower than that in the group treated with IL-37 only, and decreased when the concentration of IL-37 was 40 ng/ml.The level of PDZK1 protein in group C increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group C was lower than that in the group treated with IL-37 only, and the same concentration of IL-37 in group A and B. The values of T were 1.83, 1.37, 1.64, 1.57 ,1.49, with P values greater than 0.05. There was no significant difference between the two groups. The values of T were 1.28, 1.37, 1.26, 1.42, 1.39 in the same concentration of IL-37 in group A and C, with P values greater than 0.05, with no significant difference.The results of immunofluorescence analysis showed that the trend of the three groups was basically consistent with that of Western-Blot. Conclusion The pathogenesis of gout induced by IL-37 through PDZK1 protein may not occur at the transcriptional level, but may occur at the level of protein translation.

Expression and Clinical Significance of CXCR3 in Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of chemokine receptor CXCR3 in mantle cell lymphoma (MCL).@*METHODS@#Flow cytometry was used to detect CXCR3 in lymph nodes and extranodal tissues in 25 newly diagnosed MCL patients. The correlation of the expression of CXCR3 level with clinical features and prognostic factors was analyzed.@*RESULTS@#Twenty-five tumor submitted specimens all expressed CXCR3 at varied degrees. The expression levels of CXCR3 in lymph nodes (LN) and bone marrow (BM) were higher than those in peripheral blood (PB), and the expression intensity in BM positively correlated with the involved tumor numbers. The absolute values of lymphocytes and hemoglobins level in PB of CXCR3high group were significantly lower than those in CXCR3low group (all P0.05). The overall response rate (ORR) in CXCR3low group was significantly higher than that in CXCR3high group (P=0.001). The expression level of CXCR3 in MCL cells of the effective group was significantly lower than that before treatment (P=0.038), and the CXCR3 expression in the ineffective group was significantly higher than that before treatment (P=0.002). After following up, it was found that the 3-year overall survival (OS) time and progression-free survival (PFS) time in CXCR3high group were significantly shorter than those in CXCR3low group (all P<0.05).@*CONCLUSION@#The expression level of CXCR3 in MCL closely relates with early metastasis and prognosis. CXCR3 can be used as one of the indicators for clinical efficacy and prognosis evaluation.

Analysis of Clinical Characteivstics and Therapeutic Efticacy of 54 Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical characteristics and therapeutic efticacy of patients with mantle cell lymphoma(MCL).</p><p><b>METHODS</b>The clinical data including cliniced parameters and laboratorial test results of 54 patients with MCL were collected and restrospectively analyzed to clarity the clinical characteristics of MCL and to evaluate the survival and factors affecting prgnosis of patients.</p><p><b>RESULTS</b>The incidence of MCL accounted for 4.0% of NHL in our center. The median age of MCL patients was 63 years old, the male and female ratio was 1.4∶1. The MCL patients inⅢ-Ⅳ stage accounted for 96.3%; the extranodal organ involvement existed in 98.1% patients, the most common extranodal involvement sites were bone marrow(72.2%), spleen(51.9%), gastrointestinal tract(25.9%). The overall response rate(ORR) was 66.7%, among which the complete remisson (CR) rate was 37.1%, 3 year and 5 year-progression free survival rate was 52.7% and 34.7% respectively, 3 year and 5 year overall survival rate was 60.4% and 49.6% respectively. The therapeutic efficacy in chemotherapy combined with cytarabine group was suprior to that in chemotherapy group without cyteratine, the chemotherapy comtined with auto-HSCT could further improve the prognosis of patients. The unvariatc analysis showed that the KI67 level, B sgmptom, liver function, LDH and C-RP levels, initial therapeutic efficacy, high dose cytarabine regimen, auto-HSCT and relapse-refractroy status were prognosis-related factors; the multi-variate analysis showed that the initial therapeutic efficacy and relapse rcfractory stasus were independent prognostic risk factors. Analysis showed that the surival of patients stratified according to MIPI and MIPI-c indexes was significantly different from that stratified by IPI index.</p><p><b>CONCLUSION</b>The MCL patients commonly complicated by extranodal involvement and have poor prognoss. Using the chenotherapy regimen combined with high doge of cytarabine as induction therapy and auto-HSCT as consotidatory therapy shows the significont efficacy for survival of young patients with MCL. The MIPI and MIPIc indexe are more much suitable for prognosis evaluation of MCL patients.The initial therapeuntic efficacy and relapse-refractrong status are the independant prognosis-related factors.</p>

Clinical Features, Treatment and Prognostic Factors of 94 Patients with Follicular Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestation, therapeutic efficacy and related prognostic factors of patients with follicular lymphoma.</p><p><b>METHODS</b>A retroretrospective study was conducted on 94 patients with follicular lymphoma who were admitted to our hospital from March 1999 to June 2016. The total of 94 newly diagnosed FL patients were analyzed in terms of clinical manifestation, laboratory data, pathological examination, clinical stage and so on, so as to find out the related prognostic factors.</p><p><b>RESULTS</b>Ninety-four patients were included in this study. The median age at onset was 50.60 years old, more common in women, and ratio of male to female was 1:1.35. The superficial lymphadenopathy was found to be the first symptom in 72.3% patients, 25.5% patients had B symptoms when diagnosed, 57.4% cases had extranodal organ invasion when diagnosed, of which bone marrow invasion is the most common, accounting for 36.2%, followed by the digestive tract, bone, spleen and so on. The detected rate of BCL-2 / IGH gene rearrangement was 33.9%. Patients with grade 3 of FL accounted for 24.5%. Cases of clinical stage III-IV accounted for 71.2% in these FL patients. The overall response rate (ORR) was 92.0%, and the complete remission (CR) rate was 79.3% and the recurrence rate was 35.2%. The cumulative overall survival rates of 3, 5 and 10 years were 92.1% , 84.6% and 77.4% respectively, and the cumulative progression-free survival(PFS) rate in 3,5 and 10 years was 68.5%, 61.4% and 41.9%, respectively. The results showed that the CR rate was 85.2% in patients treated with rituximab and 69.7% in patients treated without rituximab. The OS and PFS in patients treated with rituximab were better than those in patients treated without rituximab, but there was no significant difference between them(P>0.05). Univariate analysis showed that FL stage, ECOG score, Hb and LDH levels, digestive tract involvement or not, CR or not after initial treatment had a significant impact on OS(P<0.05), while BCL-2, CD10, ECOG score, albumin, Hb and LDH levels, percentage of lymphocytes, erythrocyte sedimentation rate, digestive tract involvement had a significant impact on PFS (P<0.05). Multivariate analysis showed that digestive tract involvement or not, CR or not after initial treatment were independent risk factors for OS(P<0.05), while CR or not after initial treatment, digestive tract invdvement or not, LDH level and ECOG score were independent risk factors for PFS(P<0.05).</p><p><b>CONCLUSION</b>The FL is more common in middle-aged women, the FL was in late stage at confirmed diagnosis, bone marrow involvement is more common. The CD10 negative is poor prognostic factor for FL. The digestive tract involvement or not, CR or not after initial treatment are independent risk factors for OS, while CR or not after initial treatment, digestive tract involvement or not, LDH level and ECOG score are independent risk factors for PFS.</p>

The protective effect of environmental enrichment on radiation induced cognitive dysfunction and underlying mechanism / 中华放射医学与防护杂志

Objective To investigate the protective effect and mechanism of environmental enrichment(EE)on radiation induced cognitive dysfunction in mice.Methods A total of 45 female Kunming mice(2-month old)were randomly divided into control group,irradiation group and irradiation plus EE group with 15 in each group.Irradiation group and irradiation plus EE group were treated with a single dose of 4 Gy whole body irradiation,irradiation plus EE group were housed in EE condition for 35 d after irradiation.The object recognition task was used to evaluate the cognitive function of mice.The expression of microglial marker IBA-1 in hippocampus was determined by immunohistochemical staining.The expressions of CD68 and synaptophysin(SYP)proteins in hippocampus were assayed by Western blot.Results Compared with control group,the irradiation group had a low discrimination ratio in object recognition task and had a remarkable low level of SYP expression in hippocampus(t＝3.66,6.84,P＜0.05).In addition,radiation activated microglia in hippocampus by increasing the number of IBA-1-positive cells and enhancing the expression of CD 68(t ＝6.83,5.79,P ＜0.05).Compared with irradiation group,irradiation plus EE group increased the discrimination ratio and the expression of SYP in hippocampus(t＝3.56,4.06,P＜0.05),while the number of IBA-1-positive cells and the expression of CD68 were significantly reduced(t＝7.69,4.59,P＜0.05).Conclusions A single dose of 4 Gy whole body irradiation leads to cognitive dysfunction in mice,while EE could effectively improve the animals′cognitive behavior possibly by inhibiting microglial activation and preventing synapse loss in hippocampus.

Formaldehyde induced acute inflammation pain leads to enhanced expression of BRD 4 in spinal cord of mice / 基础医学与临床

Objective To investigate the expression of BRD 4 in the spinal cord and its relationship with acute in-flammation pain induced by formaldehyde in mice.Methods Thirty-six mice were randomly divided into three groups:control group,formaldehyde group and indomethacin+formaldehyde group;25 μL 1%formaldehyde was injected into the right plantar to establish the acute inflammationpain model,while the indomethacin(20 mg/kg) was injected intraperitoneally 1 hour before formaldehyde injection.Then,all the mice were video recored for 1h to observe the spontaneous pain.Then,cell localization of BRD4 in the spinal cord of normal mice was determined by immunofluorescence assasy.The expression of BRD4 in spinal cord was detected by immunohistochemistry and Western blot.Results Immunofluorescence showed that BRD 4 was mainly co-locolized with the neuronal marker NeuN in the spinal cord of normal mice.Formaldehyde injection could induce two-phase spontaneous pain, while indomethacin intervention could only decrease the second phase pain(P<0.05).Furthermore,formaldehyde injec-tion led to significantly enhanced expression of BRD 4 in bilateral spinal cord,which was remarkbly inhibited by in-domethacin(P<0.05).Conclusions Up-regulation of BRD4 in spinal dorsal horn may be involved in the acute in-flammatory pain.

Efficacy observation of GDP regimen for treatment of relapsed and refractory non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To analyze the efficacy of GDP regimen for treatment of relapsed and refractory non-Hodgkin lymphoma (NHL). Methods The clinical data of 40 patients with relapsed and refractory NHL in the Third Hospital of Peking University from January 2009 to June 2014 were retrospectively analyzed. All the patients underwent GDP regimen (gemcitabine, dexamethasone, cisplatin). The clinical features, laboratory data and survival status were analyzed. Results The overall response rate (ORR) of 40 patients was 67.5 ％ (27/40) with 27.5 ％ (11/40) complete remission (CR) rate and 40.0 ％(16/40) partial remission rate. The 3-year overall survival (OS) rate was 86.5 ％ and the OS rate of 5-year was 28.8 ％. The ORR and 3-year OS rate in B-cell lymphoma and T-cell lymphoma were 69.6 ％ (16/23) vs. 52.9 ％ (9/17) (P=0.283), 90.9％vs. 80.7％(P=0.480). The CR rate in patients with gastrointestinal tract involvement was better than that in patients without gastrointestinal tract involvement (P= 0.049). Meanwhile, the patients with gastrointestinal tract involvement were superior in 3-year OS rate (89.3％vs. 76.2％, but the difference was not statistically significant (P = 0.237). The major side effect was hematological adverse reactions. The incidence of grade Ⅲ/Ⅳ neutropenia was 47.5 ％, the rate of Ⅲ/Ⅳthrombocytopenia was 40.0％and the rate ofⅢ/Ⅳanemia was 17.5％. Non-hematological adverse reactions included mild nausea and vomiting. Conclusions GDP regimen is effective and well tolerated in relapsed and refractory NHL with better efficacy for gastrointestinal tract involvement NHL patients.

Efficacy of anti-CD19 CAR-T cell therapy in 10 refractory recurrent B cell malignancies / 中华血液学杂志

Objective@#To investigate the outcomes of anti-CD19 CAR-T cell for relapsed and refractory B cell malignancies. @*Method@#Ten patients with relapsed and refractory B cell acute lymphocytic leukemia (B-ALL) and non-Hodgkin’s lymphoma (NHL), diagnosed in the Department of Hematology of Peking University third Hospital from December 2015 to July 2017, were treated with anti-CD19 CAR-T cell therapy, and the efficacy and safety were analyzed. @*Results@#Efficacy was assessed on the 28th day after cell infusion, including 66.7% (4/6) of complete remission (CR) for patients with ALL, 16.7% (1/6) of partial remission (PR), and 83.3% (5/6) of overall response rate (ORR). For NHL patients, CR was 33.3% (1/3) and most of the lesions disappeared in a patient with mantle cell lymphoma, but residual lesion presented persistent state. After infusion of anti-CD19 CAR-T cells, the main side effect was cytokine release syndrome (CRS) and fever. One patient presented with aphasia and the other one had multiple organ failure, which were improved after treatment. No patients died of CRS. @*Conclusion@#anti-CD19 CAR-T cell for relapsed and refractory B cells hematological malignancies is safe, and the most problematic side effect is CRS, which can be controlled by therapy.